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Biomedical subjects

M Grandi

Publications and source records attributed to M Grandi.

At least 19 recordsLinked to original sources
PubMed2003

The detection of morphine and codeine in human teeth: an aid in the identification and study of human skeletal remains.

When studying unidentified putrefied or skeletonised human remains it may be difficult to obtain information on drug habits which may prove important for the construction of a biological profile or lead to hypotheses on the manner of death. The detection of morphine and codeine in teeth from human remains may prove crucial in obtaining such information and thus give forensic odontology and anthropology a further tool for identification. Because teeth can be an important deposit of exogenous substances accumulated both in the pulp and in the calcified tissues, they are an invaluable source of data from a toxicological point of view. The authors therefore tested 3 groups of teeth for morphine and codeine: the first group consisted of artificially aged teeth from individuals known to have died of heroin overdose; the second, of teeth from individuals with no history of drug abuse; the third, of teeth from cases of burnt, putrefied and skeletonised remains found in conditions strongly suggestive of a drug-related death. Results showed that in groups 1 and 3 morphine and codeine could still be identified in the teeth, proving that these tissues may be a reliable source for toxicological information concerning the history of the individual. Further studies are needed to verify whether the substances detected reflect drugs in circulation in an acute phase (and therefore present in blood vessels in the pulp) or whether they represent drugs which have percolated and been stored in dentine and enamel and thus denote a history of drug abuse. Nonetheless this study shows that teeth may be an important source of toxicological information in the forensic scenario.

Adult↗
PubMed2000

A computerized guideline for pressure ulcer prevention.

This paper illustrates the implementation of a computerized guideline for pressure ulcer prevention. In particular, it describes the aspects related to the site-specification of a guideline delivered by the Agency for Health Care Policy Research (AHCPR), to its integration with the electronic patient record, and to its implementation within the clinical routine. The primary goal of the system is both to facilitate nurses assessing the risk of ulcer development, and to manage patients at risk by producing daily prevention work-plans. Concerning this functionality, particular attention has been paid to manage nurse's non-compliance with the guideline suggestions and to collect data for evaluating the guideline impact. Moreover, since it is well known that nurses are often over-loaded, the human computer interaction has been studied in such a way to optimise the time spent for data input. An additional functionality of the system is the novice nurses' education - they can browse a graphical representation of the guideline, asking details about the different tasks, and they can simulate patients to obtain real-time advice. The educational tool is written in Java and it is based on a representation of the guideline as a relational database. A preliminary evaluation of the system has been performed and the results are presented on the management of about 40 patients.

Decision Support Systems, Clinical↗
PubMed1999

Determining the human origin of fragments of burnt bone: a comparative study of histological, immunological and DNA techniques.

In situations where badly burnt fragments of bone are found, identification of their human or non-human origin may be impossible by gross morphology alone and other techniques have to be employed. In order to determine whether histological methods were redundant and should be superseded by biomolecular analyses, small fragments of artificially burnt bone (human and non-human) were examined by quantitative and standard light microscopy, and the findings compared with newer biomolecular analyses based on identifying specific human albumin by ELISA and amplifying human mitochondrial DNA by PCR. For quantitative microscopy, reference data were first created using burnt bones from 15 human and 20 common domestic and farm animals. Measured osteon and Haversian canal parameters were analysed using multivariate statistical methods. Highly significant differences were found between values for human and non-human bone, and a canonical discriminant function equation was derived, giving a predicted correct classification of 79%. For the main study, samples of cortical bone were taken from three fresh cadavers, six human skeletons and ten freshly slaughtered animals and burnt by exposure to temperatures ranging from 800 to 1200 degrees C; charred fragments of human cortical bone from two forensic cases were also tested. Quantitative microscopy and canonical discriminant function gave the correct origin of every sample. Standard microscopy falsely assigned burnt bone from one human skeleton and one forensic case to a non-human source, but otherwise gave correct results. Human albumin was identified in five individuals, including one of the forensic cases, but mitochondrial DNA could not be amplified from any of the human bone. No false positive test results were seen with either biomolecular method; and human albumin and mitochondrial DNA were correctly identified in all unburnt control specimens. It was concluded that histological methods were not redundant and that quantitative microscopy provided an accurate and consistent means of determining the human or non-human origin of burnt bone and was more reliable than standard microscopy or the newer immunological and DNA techniques tested here.

Animals↗
PubMed1999

The antitumor efficacy of cytotoxic drugs is potentiated by treatment with PNU 145156E, a growth-factor-complexing molecule.

PNU 145156E (formerly FCE 26644) is a noncytotoxic molecule whose antitumor activity is exerted through the formation of a reversible complex with growth/angiogenic factors, thus inhibiting their induction of angiogenesis. We studied in vitro and in vivo the activity of PNU145156E in combination with the four cytotoxic drugs doxorubicin, cyclophosphamide, methoxymorpholinyldoxorubicin (MMDX, FCE 23762, PNU152243), and 9-aminocamptothecin against M5076 murine reticulosarcoma. In vitro, PNU 145156E did not modify the cytotoxicity of the four drugs or the cell-cycle block induced by doxorubicin. In vivo, at the optimal dose of each compound, the antitumor activity was significantly increased in all combinations, with no associated increase in general toxicity being observed. In healthy mice treated with cyclophosphamide or doxorubicin the association with PNU 145156E did not enhance the myelotoxic effect induced by the two cytotoxics. These results indicate that two drugs affecting solid tumor growth through two different mechanisms-growth factor blockage and cell proliferation can be combined, resulting in increased antitumor efficacy with no additive toxicity.

Animals↗
PubMed1999

Prevalence of HIV and hepatitis C markers among a cadaver population in Milan.

AIMS: To examine the distribution of serological markers for HIV and hepatitis C virus (HCV) infection in a medicolegal population; to compare prevalence of HIV and HCV markers and cause of death; and to evaluate the risk of potential infection to personnel involved in medicolegal incidents and procedures. METHODS: Blood samples were collected at necropsy from 328 males and 69 females, aged 16 to 50 years at time of death, and tested for antibodies to HIV and HCV. The individuals were classified according to cause of death and whether there was known antemortem risk of infection. RESULTS: Overall, 134 subjects gave positive test results: 20 for anti-HIV, 69 for anti-HCV, and 45 for both. By cause of death, the total number of positives (and negatives) with the pairs of figures referring, respectively, to patients with and without known antemortem risks were: natural causes 3 (1), 8 (32); AIDS 2 (0), 0 (0); homicide 0 (2), 5 (24); suicide 3 (0), 9 (69); road traffic accidents 1 (0), 9 (81); other accidents 2 (3), 1 (12); drug overdose 74 (17), 7 (9); unknown causes 3 (2), 7 (11). CONCLUSIONS: The cases tested represented a predominantly young male population with a high prevalence of serological markers for HIV and HCV infection. The distribution of HIV and HCV positivity varied with the cause of death, probably reflecting the known association between high risk behaviour and infection. However, a substantial number of cases with no known risks also had markers for HIV and HCV, suggesting that there is a large unrecognised pool of potential infection in medicolegal practice.

Adolescent↗
PubMed1999

Savings obtained using an oxygen economizer device: a cost-minimization analysis.

As liquid oxygen represents a relevant burden on healthcare systems, different methods have been developed to reduce oxygen consumption, including economizers. The aims of the study were: 1) to evaluate the efficacy of an economizer device (Companion 5 Oxygen Saver) in a significant sample of patients, and 2) to perform cost-minimization analysis of the possible savings to be obtained using the device. The study was designed as an open, prospective clinical trial in which equivalence in haemoglobin saturation with and without the economizer device was demonstrated, preliminary to cost-minimization analysis in patients affected by restrictive and obstructive lung disease. Patients were to use their usual O2 flow, provided it was able to guarantee a saturation of > or = 90% and an arterial oxygen tension (Pa,O2) of > or = 8.0 kPa (60 mmHg) during rest, sleep and exercise with and without the economizer (mean value and different saturation ranges compared by means of parametric or nonparametric tests where appropriate). The average unit cost was calculated with and without the economizer, based on the average unit O2 consumption, and cost-minimization analysis was performed. In 29 patients enrolled, the mean (+/- SD) O2 flow in L.min-1 was 1.5 +/- 0.6 during sleep, 1.4 +/- 0.6 during rest and 2.3 +/- 1.1 during exercise. The mean oxygen saturation during sleep was 91.2 +/- 19.5% without and 97.2 +/- 3.9% with the economizer device (p = 0.09), the mean saturation during rest was 88.8 +/- 22.7% without and 92.1 +/- 14.9% with the economizer device (p = 0.42), and the mean saturation during exercise was 84.7 +/- 19.3% without and 91.8 +/- 15.9% with the economizer device (p = 0.04). The total daily O2 consumption was significantly lower using the economizer device (2,384 +/- 950.3 versus 93.0 +/- 482.9 L, p < 0.001). The potential savings, estimated per patient per year, were 530,114 +/- 184,233 L, corresponding to US$2,492 +/- 866. During the first year the total unit savings would be US$1,892. The savings, consistently relevant alongside the whole range of variation explored by sensitivity analysis both during the first and the following years, justify considering the adoption of similar economizers on a larger scale, although further studies should be performed to evaluate whether or not liquid oxygen really represents the most cost-effective method of treating hypoxaemic patients.

Aged↗
PubMed1999

A computerised guideline for pressure ulcer prevention.

This work illustrates the implementation of a computerised guideline for the pressure ulcers prevention. In particular, we describe the site-specification of a guideline delivered by the Agency for Health Care Policy Research, its integration with the electronic patient record, and its introduction within the clinical routine. The system facilitates trained nurses in the patient management by producing daily workplans, and novice nurses by running as an educational tool.

Humans↗
PubMed1998

Silicone rubber/hydrogel composite ophthalmic inserts: preparation and preliminary in vitro/in vivo evaluation.

The present report describes the development and in vitro/in vivo testing of rod-shaped mucoadhesive ophthalmic inserts fitting the upper or lower conjunctival fornix. Cylindrical devices (diameter 0.9 mm, length 6-12 mm, weight 3-8 mg) all containing 0.8 mg oxytetracycline HCl (OXT) were prepared from appropriate mixtures of silicone elastomer, OXT and sodium chloride as release modifier. A stable polyacrylic acid (PAA) or polymethacrylic acid (PMA) interpenetrating polymer network (IPN; 30 or 46% w/w) was grafted onto the inserts' surface by treatment with a mixture of acrylic (or methacrylic) acid and ethylene glycol dimethacrylate in xylene at 100 degrees C. Mucoadhesion studies in vitro showed that the mucoadhesive properties increased significantly with increasing thickness of the IPN layer. The inserts were tested for drug release in vitro, and for drug release and retention in rabbit eyes. The presence of IPN, as well as of NaCl, in general increased the drug release rate. The PMA-grafted devices released OXT at lower rates when compared with the PAA-grafted ones. A nearly zero-order release rate for about 1 week was observed in vitro for some types of inserts. When tested in rabbits, some IPN-grafted inserts maintained in the lacrimal fluid a OXT concentration of 20-30 microg/ml for several days: the in vitro minimum inhibitory concentration values (MIC 90%) of OXT against micro-organisms responsible of common ocular infections range from 0.8 to 2.0 microg/ml, while MIC 90% values in the range 14-50 microg/ml have been indicated for Pseudomonas aeruginosa. The ocular retention of IPN-grafted samples was significantly higher with respect to ungrafted ones. The presently described mucoadhesive silicone inserts might prove efficient therapeutic systems for chemotherapy of ocular bacterial infections, such as trachoma.

Animals↗
PubMed1998

[Erythrocytosis in patients with hepatocarcinoma in alcoholic cirrhosis: ectopic production of erythropoietin?].

We report the case of a patient with alcoholic liver cirrhosis and generalized atherosclerosis who rapidly developed erythrocytosis. Concomitantly we documented a significative and progressive increase of serum Erythropoietin (Epo) and a small focus of hepatocellular carcinoma (HCC) never diagnosed before. Even in absence of immunohistochemical and/or biomolecular evidence of Epo production in the neoplastic tissue we think the hypothesis of the paraneoplastic syndrome may be the most likely both for the strict temporal relationship between the observation of the neoplastic lesion and the appearance of polycythemia and for the absence of all other known causes of erythrocytosis. Objection to this hypothesis: 1) ectopic production of Epo during HCC has been usually described in large neoplastic lesions 2) liver cirrhosis by itself may be accompanied by increased Epo levels 3) an intratumoral hypoxia with compensatory production of Epo may have occurred 4) generalized vasculopathy could have determined renal hypoxia with greater local production of Epo.

Aged↗
PubMed1997

Effect of acute carnitine administration on glucose insulin metabolism in healthy subjects.

The authors evaluated the effect of carnitine on glucose insulin metabolism. Twenty-five subjects free from metabolic disorders or serious functional alterations in the liver, kidneys or myocardium were studied. All were infused with a 5% glucose-enriched solution (Group A); 48 h later the same subjects were infused with a 5% glucose solution containing 2g carnitine (Group B). Variations in blood glucose and insulin levels and range were measured at different times during and after infusion. Study results showed that the administration of carnitine lead to an improvement in glucose metabolism, as demonstrated by a saving in insulin secretion accompanied, at least on a temporary basis, by a corresponding decrease in blood glucose which, however, remained within normal parameters.

Adult↗
PubMed1996

Morpholinylanthracyclines: cytotoxicity and antitumor activity of differently modified derivatives.

The relationship between different chemical modifications on morpholinylanthracyclines and their ability to overcome multidrug resistance (MDR) has been evaluated testing all compounds in vitro on LoVo and LoVo/DX human colon adenocarcinoma cells and in vivo disseminated P388 and P388/DX murine leukemias. Results obtained led us to the following conclusions: 1) the insertion of the morpholinyl or the methoxymorpholinyl group on position 3' of the sugar moiety confers the ability to overcome MDR in vitro and in vivo; conversely, 4' morpholinyl compounds are effective on MDR cells only in vitro and result inactive in vivo on DX-resistant leukemia; 2) all chemical modifications performed on 3' morpholinyl or methoxymorpholinyl derivatives, that is substitutions on the aglycone or on position 2 of the morpholino ring, do not interfere with the activity of the compounds: all derivatives present in fact the same efficacy on sensitive and resistant models. It is concluded that position 3' in the sugar moiety plays a crucial role in the ability of morpholinyl-anthracyclines to overcome MDR.

Adenocarcinoma↗
PubMed1995

Antitumor activity of FCE 26644 a new growth-factor complexing molecule.

FCE 26644, or 7,7'-(carbonyl-bis[imino-N-methyl-4, 2 pyrrole carbonyl-imino(N-methyl-4,2-pyrrole)carbonyl-imino])-bis-(1,3- naphthalene)disulfonic acid, belongs to the newly synthesized class of sulfonated derivatives of distamycin A. FCE 26644 is a noncytotoxic molecule capable of inhibiting the binding of basic fibreblast growth factor (bFGF), platelet-derived growth factor (PDGF beta) and interleukin 1 (IL-7) to their receptors and to block bFGF-induced vascularization in vivo as well as neovascularization in the chorioallantoic membrane. FCE 26644 and suramin, a compound possessing the same terminal half-life (t1/2) in mice and, presumably, the same mode of action, inhibit the growth of solid murine tumors, M5076 reticulosarcoma, and MXT and S180 fibrosarcoma and are inactive against B16F10 melanoma. The activity of FCE 26644 was constantly observed at nontoxic doses, at variance with suramin. FCE 26644 was also found to maintain activity against M5076 resistant to cyclophosphamide and to be equally active against UV 2237 and UV 2237/ADR fibrosarcoma.

Animals↗
PubMed1995

Decreased tyrosine phosphorylation in tumour cells resistant to FCE 24517 (tallimustine).

Resistance to FCE 24517 is not related to the emergence of any of the most frequently observed phenotypes. We have found that two resistant cell lines (L1210/24517 murine leukaemia and LoVo/24517 human colon adenocarcinoma) present congenital modifications in tyrosyl phosphatase and kinase activities. Moreover, the cytotoxic activity of FCE 24517 is increased in combination with a tyrosine phosphatase inhibitor and decreased in combination with protein kinase inhibitors, this being in agreement with the hypothesis that the activity of this drug is strictly dependent on the presence of tyrosine phosphorylated protein(s).

Adenocarcinoma↗
PubMed1995

Timing of tracheostomy in neuromuscular patients with chronic respiratory failure.

Noninvasive and invasive mechanical ventilation play a fundamental role in the treatment of neuromuscular patients with respiratory failure. At present no guidelines concerning timing of tracheostomy in neuromuscular patients are available. The authors summarize the factors to be considered in the decision-making process, as illustrated during an international meeting (Tradate, Italy; March 1994) held with the participation of a group of authorities on respiratory care of neuromuscular patients.

Humans↗
PubMed1995

FCE 27266, a sulfonic distamycin derivative, inhibits experimental and spontaneous lung and liver metastasis.

FCE 27266, 2,2,'-(carbonyl-bis(imino-N-methyl-4,2-pyrrole carbonyl-imino¿N-methyl-4,2-pyrrole¿carbonylimino])-bis- (1,5-naphthalene) disulfonic acid, is a noncytotoxic compound able to complex bFGF, PDGF beta, IL-8, VEGF and IL-1 beta and to inhibit the binding to their receptors. A single intravenous treatment 48 h prior to intravenous injection with tumor cells was associated with 60% inhibition of lung metastasis from B16F10 murine melanoma and 82% inhibition of liver metastasis from M5076 murine reticulosarcoma. Marginal inhibition was observed in the latter model, administering the drug 24 h after tumor cell injection. Efficacy was maintained in athymic mice, with 95 and 100% inhibition of lung metastasis from B16F10 melanoma and A375 human melanoma. The antimetastatic activity was confirmed in two models of spontaneous metastasis: in Lewis lung carcinoma implanted intramuscularly, daily intraperitoneal treatment from day 1 to 17 was associated with 77% inhibition of lung metastasis; on M5076 reticulosarcoma implanted intramuscularly, daily intraperitoneal treatment from day 1 to 14 prior to amputation of the tumor was associated with significant inhibition of liver metastasis (79%); conversely, daily intraperitoneal treatment from day 15 to 28 starting 1 day after amputation was marginally effective. The administered doses did not inhibit the growth of the primary tumor in both models. It is concluded that FCE 27266 is a novel, promising molecule, with significant efficacy on lung and liver metastases of murine and human origin; its mode of action is still under study and is probably exerted through inhibition of growth factors and cytokines influencing the different steps of angiogenesis and metastasis.

3T3 Cells↗
PubMed1994

New sulfonated distamycin A derivatives with bFGF complexing activity.

Tumor-induced neoangiogenesis is an essential event for solid tumor growth. Therefore, a compound able to block angiogenesis-promoting factors could have antitumor activity. The polysulfonated naphthylurea suramin is hypothesized to have this mode of action. A series of sulfonated distamycin A derivatives have been synthesized with the objective of identifying novel compounds able to complex basic fibroblastic growth factor (bFGF) and other factors involved in tumour angiogenesis, and consequently to block the angiogenic process. These new compounds have been characterized for their ability to inhibit bFGF binding, in vivo bFGF-induced angiogenesis and neovascularization of the chorioallantoic membrane, in comparison with suramin. The two most active compounds, FCE 26644 [7,7'-(carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2- pyrrole)carbonylimino))-bis(1,3-naphthalenedisulfonic acid)] and FCE 27164 [7,7'-(carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2- pyrrole) carbonylimino)-bis (1,3,5-naphthalenetrisulfonic acid)] have been selected for extended evaluation. Both compounds are active in inhibiting platelet-derived growth factor beta (PDGF beta) and interleukin-1 beta binding. Two different assays have been performed to study their mode of action: the sequential binding assay on bFGF and PDGF receptors and the bFGF-induced tyrosine phosphorylation assay. The results of the two assays are in agreement and indicate that no activity is observed if FCE 26644, FCE 27164 and suramin are administered as pretreatment, when a direct interaction of the compounds with bFGF and PDGF receptors is required. Conversely, inhibitory activity is observed when the compounds are allowed to form complexes with the growth factors themselves.

3T3 Cells↗